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Dear Sir,

First, we would like to thank Levy and co-workers for their interest in our review on cardiovascular disease induced by radiotherapy. The comment that pentoxifylline is suggested to prevent radiation-induced cardiotoxicity is indeed very interesting [1]. Unfortunately, in our review, we were only able to mention a few potential targets of treatment to ameliorate radiation-induced tissue damage [2]. The ability to treat chronic inflammation by targeting nuclear factor kappaB (NF-kappaB) has been suggested for a number of available drugs, but there is a paucity of therapeutical adjuncts suggested to cope with the adverse effects of radiotherapy. The involvement of the transcription factor NF-kappaB in a plethora of cellular activities has made it one of the most studied proteins during the last decade [3]. It is therefore of utmost interest that the effects of pentoxifylline has been studied even beyond NF-kappaB in the context of radiation-induced inflammation. In a previous study, we undertook a global gene expression strategy to study differential gene expression patterns by comparing irradiated human conduit arteries with nonirradiated controls from the same patient, both harvested during microvascular free tissue transfers for cancer reconstruction [4]. With gene ontology tree machine analysis, in a subset of the material, we could identify not only an innate immune response but also transcription favouring increased fibrosis and ischemia. The findings were similar to what has been shown in other tissues but were for the first time shown in human blood vessels. Furthermore, the results revealed an increase not only in HIF1A and MMPs but also in IL-6- and TNF-alpha-related proteins where pentoxifylline, according to Levy et al., seems to have a promising cause of action beyond NF-kappaB in the context of radiation-induced cardiovascular disease. However, whether the mentioned results from irradiated hearts of rats can be extrapolated to include human conduit arteries needs to be further investigated. Furthermore, the promising possibility that pentoxifylline can prevent heart failure and symptomatic coronary heart disease in humans needs to be tested in future randomized trials.

Conflict of interest

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No conflict of interest was declared.

References

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